Mycoplasma is known to infect animals such as human, domestic animals, and pets, and to cause various diseases. Particularly, in human, mycoplasma is believed to be strongly associated with not only pneumonia, but also respiratory diseases caused by chronic or repetitive mycoplasma infection such as asthma and chronic obstructive pulmonary disease (COPD), rheumatic diseases such as rheumatoid arthritis (Non-patent Document 1), and neural diseases such as multiple sclerosis, and currently most potential candidate as a causative microorganism for these chronic diseases called intractable diseases (FIG. 1, and Non-patent Documents 31 and 32).
Cases of Mycoplasma infection that stemmed from cold symptoms such as fever, cough, and pneumonia, and developed into asthma, chronic obstructive pulmonary disease (COPD), multiple sclerosis, or a rheumatic disease are known. At the time, it is known that reactivation or exacerbation of the symptoms repeats and transfers gradually to a chronic disease, and thus along with early diagnosis and early treatment, prevention or treatment of exacerbation (gradual aggravation of the symptoms) or reactivation (aggravation of the symptoms again after the symptoms become less severe once) are especially important.
However, with a conventional examination method, it was difficult to grasp diagnosis of mycoplasma infection or progression of treatment for mycoplasma infection. Thus, details for the diagnosis of mycoplasma infection or the progression of treatment for mycoplasma infection are not clarified, and therefore, the present situation is that there are many patients who receive no appropriate prevention or treatment. A diagnosis method for mycoplasma infection that is most widely used currently is a serum diagnosis method. However, the conventional diagnosis method is an antibody assay method by culturing Mycoplasma pneumoniae in a large amount, and using a crude extract from a fungus body thereof, and thus has problems in specificity, detection sensitivity, and quantitative property, and has difficulty in early diagnosis of mycoplasma infection.
The present inventors focused attention on a lipid antigen on the surface of various bacteria belonging to a mycoplasma genus, and discovered multiple kinds of lipid antigens specific to respective bacterium from the past. The present inventors succeeded in separation, purification, and structure-determination of these specific lipid antigens, and also succeeded in chemical synthesis for some of the lipid antigens (Patent Documents 1 to 8).
Diagnostic products using these specific lipid antigens for mycoplasma infection have high specificity and sensitivity in comparison with existing diagnostic products, and lead to establishment of a quantitative measurement method for the change of the antibody titer, and it can be said that early diagnosis for mycoplasma infection, which has been a problem so far, can be tentatively resolved.
However, a therapeutic agent for mycoplasma infection that is in practical use as a therapeutic agent that can be currently most expected for the treating effects, is some antibiotics such as macrolide-based, or newquinolone-based, or tetracycline-based antibiotics, but such antibiotics have great adverse effects, and also have big problems such as advent of drug-resistant strains, which leads the mycoplasma infection to become severe while sufficient treating effects are not expected, and becomes a cause for transfer to a chronic disease.
On the other hand, a vaccine therapy for mycoplasma is not developed for human. The reasons therefor are that a live vaccine, an attenuated vaccine, and the like have problems in safety and are difficult to practically use, and a killed vaccine or the like has a problem of an allergic reaction by contamination of a horse serum in a culture fluid, and the like. In addition, an example of the reason is that identification of efficacious, specific antigen protein is not possible yet even with progress of peptide or DNA analysis in order to specify a specific antigen protein that leads to vaccine induction. As for a vaccine for domestic animals such as a pig or a cow, live vaccines, attenuated vaccines, or the like, conventionally used are under further improvements (Patent Documents 9 to 12). A vaccine using a protein antigen was also developed (Patent Documents 13 to 15). Recently, a vaccine that was targeted to an enzyme that was associated with tissue damage by mycoplasma infection, was developed (Patent Document 16). However, all of these vaccines only have effects of suppressing pneumonia, or effects of suppressing inflammation, and cannot be said to be a vaccine having small toxicity and being effective even as a vaccine for domestic animals.
As described above, an effective prevention or treatment method for mycoplasma infection was rarely found conventionally, and thus there is an urgent need for development of an effective preventive or therapeutic agent for mycoplasma infection, particularly, a vaccine for mycoplasma infection.
In the meantime, it is known that in production of a vaccine in various pathogenic virus, target's pathogenic virus-mimic particles are prepared, and immunization is conducted using the virus-mimic particles whereby to obtain high immune response. In addition, development of a vaccine preparation having high activity and high safety using the virus-mimic particles is also in progress (Non-patent Document 2). A vaccine incorporated into a liposome and the like in an antigen peptide of virus are also in a direction to practical use (Non-patent Document 3).
A virus self-duplicates a structure protein, an enzyme, and the like using a cell mechanism, coats a membrane of the cell, and goes out of the cell and grows. Consequently, a virus has no lipid antigen in a cell membrane, and most of vaccines are from a virus particle or a protein antigen. A virus has extremely small size, and also has small structural components on the surface, and thus it is relatively simple to imitate virus particles, i.e., provide virus-mimic particles that are mistaken as invasion of virus itself by the immune system of an organism.
On the other hand, bacteria including mycoplasma can self-duplicate by DNA, and produces basically unique structural components of a lipid membrane, and thus the membrane lipid component is specific to a respective bacterium, and complicated. Consequently, it is difficult to analyze structural components of a cell membrane or membrane lipids, and in further consideration of a wide variety of cell components, membrane proteins, and the like, it is difficult to conceive of mimicking mycoplasma itself simply with only one component among them, and thus the concept of mycoplasma-mimic particles or bacterium-mimic particles was not familiar. Usually, it is unclear which component among these many components remains as essential, and how to provide mycoplasma-mimic particles using a particle preparation technique, and it is unclear whether such mycoplasma-mimic particles cause immune response enough for mycoplasma infection and mistaking of the biological immune system.